Epilepsy is a potentially debilitating disease that afflicts at least 2% of the population. Using the hippocampus as the experimental model for epilepsy, and principally the in vitro slice preparation, the overall aim of this proporal is to make a significant step towards furthering our understanding of the cellular basis of epileptogenesis. Experiments will be designed that attempt to answer the following questions: What is the paroxysmal depolarizing shift (PDS; the intracellular correlate of the interictal discharge)? What controls the PDS frequency and duration? What is the sustained depolarizing shift (SDS; the intracellular correlate of the seizure)? What controls the transition from the PDS to SDS? and Are the epileptogenic factors involved in genetically associated chronic models of epilepsy similar to those in acute drug induced epilepsy models? The experiments will be accomplished using state-of-the-art techniques of cellular neurophysiology, neurochemistry and neuroanatomy which will enable us to investigate the active and passive membrane properties of hippocampal neurons, as well as the synaptic microphysiology of their interconnections. The results of the physiological experiments will be incorporated into computer models of single cells and small groups of cells in an attempt to reconstruct functionally the normal and epileptogenic behavior of hippocampal neurons. The success or failure of the computer simulations to mimic the behavior of the neurons will provide insight for further experimentation.